- Painful stimuli cause changes in a network of brain regions called the Pain Matrix. But
most of these regions respond to many other stimuli, not just pain. Researchers want to
understand how different factors influence pain. They want to test what happens when people
expect different levels of pain and receive treatments that can modify pain. They want to see
if these factors influence decisions about pain and how the body responds to it. They also
want to compare pain with responses like taste and vision.
- To better understand how pain and emotions are processed and influenced by psychological
- Healthy volunteers ages 18 50.
- This study requires 1 to 2 clinic visits that last 1 to 3 hours.
- Participants will be screened with medical history and physical exam.
- Some participants will have one or more magnetic resonance imaging (MRI) scans of their
brain. For MRI, participants will lie on a table that slides in and out of a cylinder.
The scanner makes loud knocking noises. They will get earplugs.
- Participants heart activity will be recorded with electrocardiogram. Their pulse,
sweating, and breathing will be monitored.
- Some participants will take a taste test. Others may perform simple tasks. Others may
receive pain in their arm, leg, or hand. The pain will come from heat or electric
shocks. Others may judge pain using a topical pain-relieving cream. Some of these tests
may be given during MRI.
- Participants will fill out questionnaires.
- The study will last 3 years.
Pain is one of the most important signals for an organism s survival. The pathways that
transfer noxious input from the periphery to the central nervous system are highly conserved
across human and animal models. In humans, the ultimate experience of pain is also highly
influenced by psychological factors. For example, the placebo effect leads to robust pain
relief and can influence responses to noxious stimuli in the human brain. However, the
psychological and neurobiological mechanisms by which psychological factors influence pain
remain largely unknown.
Pain can be modulated by explicit beliefs about treatments, prior experience and learning,
interpersonal processes that support the patient-provider relationship, and contextual
factors related to the treatment environment. In the proposed series of experiments, we will
systematically investigate the neural and psychological mechanisms that mediate the effects
of these factors on acute pain. We will focus on expectations, attention, emotion,
conditioning/associative learning, and social factors. These experiments will principally use
functional magnetic resonance imaging (fMRI) and psychophysiological measurements, as well as
behavioral assays and self-reports. We will examine the effects of different types of
pain-related expectations on decisions about pain as well as responses in the brain and
periphery. We will also compare acute pain with other hedonic and perceptual processes. This
will allow us to distinguish processes that are unique to pain perception from those that are
not specific to pain, such as processes involved in perception and decision-making across
Together, the proposed series of experiments aim to elucidate the psychological,
neurobiological, and physiological mechanisms that modulate pain. This, in turn, can identify
targets for pain treatment and inform mechanistic studies of altered pain processing in
We plan to recruit 280 healthy volunteers between age 18 and 50.
The aim of the proposed series of experiments is to understand how expectations, attention,
and emotion influence acute pain. We will manipulate expectations about noxious stimuli using
associative learning and verbal instructions, in both within-subjects and between-groups
designs. We will measure decisions about pain experience (self-report) as well as neural and
physiological responses to noxious stimuli that cause pain. We will combine computational
modeling with advanced neuroimaging analyses to isolate the neural and psychological
mechanisms that mediate the effects of expectations, attention, and emotion on subjective
pain. To determine the specificity of these mechanisms, we will compare acute pain modalities
(e.g., thermal pain versus shock-induced pain), and we will contrast pain with other hedonic
and perceptual domains (e.g., taste).
Dependent variables for all experiments will include decisions about pain and/or other
percepts (e.g., sweetness of a taste) measured with visual analogue scales, reaction time,
physiological responses (e.g., skin conductance, pupil dilation), and/or BOLD activation in
regions of interest. We are specifically interested in processes within the network of
regions known to be involved in pain processing (pain-processing network, PPN), as well as
responses in the prefrontal cortex (PFC), ventral striatum (VS), and amygdala. We hypothesize
that nociceptive stimuli and pain ratings will be associated with unique patterns of
activation within the PPN, whereas responses in regions associated with value, executive
function, and decision-making will be common across outcomes.
- INCLUSION CRITERIA:
- Between 18 and 50 years old
- Fluent in English
- Able to provide written informed consent.
- Unable to comply with study procedures or follow-up visits.
- Has a major medical condition or medical history that in a clinician's assessment
could affect heat sensitivity, pain thresholds, or ability to comply with study
procedures. This may include cardiovascular, autonomic, neurological or psychiatric
conditions (including stroke and blindness or deafness, a history of brain damage,
substance or alcohol dependence or abuse or psychosis) or a chronic systemic disease
- Has a medical condition that in a clinician's assessment might affect somatosensation
(e.g., Raynaud s disease, peripheral neuropathy, or circulatory disorder).
- Has a current chronic pain condition or has had chronic pain in the past (painful
condition lasting more than six months).
- Has a dermatological condition such as scars or burns, or has had a tattoo in the
testing region within the previous 4 weeks that might influence cutaneous sensibility.
- Regular use of prescription medication that has a significant effect on pain or heat
perception. Excluded medications include central-acting agents such as opiates
(morphine, tramadol), antidepressants (amitriptyline, duloxetine, milnacipran),
anticonvulsants (gabapentin, pregabalin), anxiolytics (barbituates, benzodiazepines),
hypnotics (zolpidem, sodium oxybate), antipsychotics (valproate, lithium, olanzapine),
antimigraine agents (sumatriptan, ergotamine), and muscle relaxants (cyclobenzaprine,
carisoprodol). Use of analgesic medications, such as non-steroidal anti-nflammatories,
salicylates, and acetaminophen, taken on an "as needed" basis is acceptable as long as
the last dose taken was within 5 half-lives of testing.
- Used recreational drugs within the past month.
- Is pregnant.
- NCCIH employees.
- Participation in an NIH study of analgesia, as gleaned from CRIS.
- Individuals with conditions that could pose a risk relating to the safety of the fMRI
procedure or pain stimulation will be excluded from the MRI portion of the protocol,
but may participate in the non-fMRI sessions (with the exception of pregnant women).
Such conditions include:
- Those with ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip,
implanted neural stimulator, cochlear implant, ocular foreign body.
- Those with an abnormality on a structural MRI.
- Those with an implanted cardiac pacemaker or auto-defibrillator.
- Those with an insulin pump.
- Those with an irremovable body piercing.
- Pregnant women (based on urine test completed within 24 hours prior to scan).
- Individuals who are left-handed (based on self-report or score on handedness
questionnaire) will be excluded from fMRI substudies.